Genomic Medicine Implementation Unit

National Human Genome Research Institute

Investigators

Abstract

This project is focused on translating genomic knowledge into improved diagnosis, treatment, and prevention in rapidly evolving areas of genomic medicine such as pharmacogenomics, undiagnosed Mendelian conditions, and actionable secondary findings from genomic sequencing and other genetic testing. While we plan to integrate our work with that of other CPHR Principal Investigators, serving as the implementation arm for their translatable findings, this year we have tabled our plans for a Genomic Medicine Cohort due to lack of funding. We continue to explore potential collaborations in genomic medicine consultation with two area medical centers, and to examine the ancestral diversity of genomic databases used to produce the Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines. The Genomic Medicine Cohort, now on hold, is intended to be a cohort resource of 5,000 individuals who express an interest in augmenting their health care by precision healthcare tools (such as exome or genome sequencing or gene panel testing) and who consent to data sharing, re-contact, and longitudinal follow-up. Various state-of-the-art omic and informatics tools may be applied to cohort members to, for example, identify pre-symptomatic risks, examine potential etiologic and pathophysiologic implications of these findings, and potentially customize treatments for existing or identified conditions. The primary objective is to assess the usefulness for participants and their providers of omic and informatic approaches to healthcare in a racially and ethnically diverse cohort of individuals interested in participating in precision health research. To date we have drafted an initial protocol for IRB submission but have not finalized it pending the availability of dedicated funding and staff. We have continued to develop collaborations with Frederick Health Hospital, establishing a monthly Genomics Case Conference that is growing in attendance and interest from Frederick non-genetics providers. We are also exploring a new potential collaboration with the University of Maryland in testing and reporting of genomic sequence variation. Potential collaborations with Howard University Hospital remain on hold during their transition to a new Dean and genetics department chair. We have continued our efforts to examine racial/ethnic differences in the type and frequency of actionable variants in pharmacogenes (genes whose products control critical pathways in drug absorption, distribution, metabolism, excretion, and response) using allele frequency data from the Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines. This builds upon our prior work assessing frequency of pharmacogenetic (PGx) variants in Latino and Indigenous American populations as catalogued by CPIC guidelines for 11 PGx genes classified for normal or altered function. In that work we demonstrated the marked underrepresentation of these populations in the data used to generate CPIC guidelines as well as a nearly 5-fold higher frequency of altered function alleles in Latino and Indigenous American populations than in European populations. We have expanded our exploration of these race/ethnic differences to other underrepresented groups reported in CPIC guidelines and have nearly finalized a manuscript reporting these findings.